**5. The fetus and fetal complications: "pandora's box"**

The negative outcome of pregnancy in patients with SLE is always due to complications due to abortion, premature birth, and neonatal lupus. We know that this incidence has a multifactorial origin.

In the high-risk pregnancy controls of these women, certain protocols emanating from the existing guidelines and, of course, from the evidence must be adhered to, adjusting the frequency of fetal surveillance according to the maternal and/ or fetal status [35]. Fetal surveillance is assessed based on biometry and Doppler ultrasound findings of the umbilical and uterine arteries at 20–24 weeks, since it is extremely valuable data for pregnancy disorders associated with the placenta, such as preeclampsia and IUGR, especially the distinction between early and late, since this will help us to adapt at the time of delivery and thus reduce perinatal morbidity and mortality. The mode (vaginal vs. cesarean section) and timing of delivery are influenced by maternal factors (hypertensive disorders and anticoagulation status) as well as fetal conditions during pregnancy [3].

Neonatal lupus syndrome compromises several organs, where skin involvement can be present at birth, or appear between 4 and 6 weeks of age in the form of erythematous, photosensitive, and ring-type lesions. As the first days of birth go by, the concentrations of maternal antibodies decrease, and with this, they are resolved without major problem. We can also find liver involvement that includes liver enzyme profile without clinical expression, mild hepatosplenomegaly, cholestasis and hepatitis, hematological with manifestations such as anemia, neutropenia, thrombocytopenia and, rarely, aplastic anemia. In a small cases, central nervous system involvement such as changes in white matter, calcification of basal ganglia, and hydrocephalia [36].

The case is different in cardiac compromise because despite being able to have evidence of a structurally healthy heart, the damage produced in the conduction system is usually irreversible. Fetal echocardiography is especially indicated in the context of the presence of maternal anti-Ro/SSA or anti-La/SSB antibodies due to the risk of congenital heart block (CHB), which reaches a rate of 16%. The suggestion accepted so far is to perform weekly fetal echocardiograms from week 16, with great reservations because it is still unknown if it is a truly cost-effective measure that is applicable to all women regardless of whether or not they are at risk of the fetal congenital block, in order to perform screening of these patients [37].

CHB is the most severe manifestation of neonatal lupus. Its pathophysiology is well-documented, where the transplacental passage of maternal antibodies (anti-Ro (Ro52) and Anti La) is related to direct damage to the fetal conduction system from approximately 18 to 25 weeks. The prevalence of CHB is 2% of cases in women with detected anti -Ro antibodies and 10-20% of cases with history of a child with previous pathology. Clinical findings are related to arrhythmias and conduction system abnormalities, such as complete atrioventricular blocks, fetal bradycardia and/or congestive heart failure, premature atrial contractions, pericardial effusion, or tricuspid regurgitation [38]. More than half of the children born with this pathology require the urgent insertion of a pacemaker since it is a life-threatening condition. The most accepted theory is that CHB originates from chronic inflammation of the fetal conduction tissue that mainly affects the atrioventricular node. Histology reports have found lymphocytic infiltrates, antibody and complement deposits, calcification, and fibrosis. It is believed that the presence of maternal antibodies goes hand in hand with autoimmune diseases, such as SLE and Sjogren's syndrome, although it also occurs in women who do not apparently have any disease that explains this association in the fetus. The antigenic components of the antibodies have shown the existence of almost 100% of these directed to the RO-52 protein. Ro60 and anti-La antibodies are also related to CHB to a lesser extent. There are other antibodies that also participate, such as antibodies against muscarinic acethylcoline receptor of neonatal heart. Calreticulin has been indicated as an additional serological marker and is closely related to Sjogren's syndrome [39].

Prenatal therapy with fluorinated steroids (FSs) is performed in cases of incomplete heart block, although evidence indicates that its use in many cases did not prevent the progression of the block and the subsequent need for the use of pacemakers (**Figure 4**).

Therapy with FS can be started as long as both fetal (IUGR and oligohydramnios) and maternal side effects (infections, osteoporosis, osteonecrosis, and diabetes) vs. beneficial effects are taken into account. In a French cohort, it was determined that the use of FS was not associated with CHB regression or increased survival, despite evidence showing positive effects on cardiomyopathy, endocardial fibroelastosis, and hydrops fetalis [41].

In the European and American cohorts, no conclusion was found that could direct treatment. The prognosis after pacemaker placement in children is excellent. In another multicenter study, the combination with FS plus immunoglobulin and plasmapheresis was performed, where better results were obtained compared to those treated with corticosteroids alone. However, in another series, encouraging results were not obtained in relation to the efficacy of monotherapy with IVIG or plasmapheresis.

Regarding treatment, a survey was conducted by the organizing committee of the ninth International Conference on Reproduction, Pregnancy, and Rheumatic Diseases. *Fertility, Pregnancy, and Systemic Lupus Erythematosus DOI: http://dx.doi.org/10.5772/intechopen.107036*

#### **Figure 4.**

*Response in degrees of blockade to therapy with FSs [40].*

#### **Figure 5.**

*Buyon scheme for the management of CHB.*

For first grade is recommended start treatment with dexamethasone or hydroxychloroquine. For the second degree, dexamethasone was recommended. For third grade, starting dexamethasone or IVIg was recommended, although a percentage (27%) would no longer start treatment. Dr. Jill Buyon, who is an expert on the subject, recommends a treatment scheme according to the weeks of gestation together with the performance of the fetal echocardiogram (**Figure 5**) [42].

Complications associated with neonatal antiphospholipid antibodies: the most frequent are prematurity and IUGR. These patients have a worse pregnancy outcome and neonatal outcome if they already have a history of thrombosis. Antiphospholipid thrombosis is unusual in the newborn or fetus despite the transplacental passage of antibodies.
